Susceptibility and Resilience to PTSD-Like Symptoms in Mice Are Associated with Opposite Dendritic Changes in the Prelimbic and Infralimbic Cortices Following Trauma.
PTSD-like state; dendritic morphology; prelimbic and infralimbic cortices; susceptibility and resilience
Abstract :
[en] Post-traumatic stress disorder (PTSD) is triggered by exposure to traumatic events, but not everyone who experiences trauma develops this disorder. Like humans, PTSD-like symptoms develop in some laboratory rodents (susceptible individuals), while others express less or no symptoms (resilient individuals). Here, considering (i) the putative causal role of fear conditioning in PTSD development and (ii) the involvement of the medial prefrontal cortex (mPFC) in the regulation of conditioned fear response, we tested whether trauma-associated changes in the mPFC may discriminate stress-resilient from stress-susceptible mice. From data on avoidance behavior (as a major symptom), we found that trauma-exposed mice displayed a bimodal distribution in their step-through latency, with low avoider (stress-resilient) individuals and high avoider (stress-susceptible) individuals. Dendrites of Golgi-Cox-stained neurons were analyzed in two parts of the mPFC: the prelimbic (PrL) and infralimbic (IL) areas. In the resilient phenotype, the total number of dendrites decreased in the PrL and increased in the IL; however, it decreased only in the IL in the susceptible phenotype compared to controls. These findings demonstrate that the type of post-trauma morphological changes in the mPFC is associated with susceptibility or resilience to trauma-related symptoms.
Bentefour, Yassine ; Université de Liège - ULiège > Neurosciences-Neuroendocrinology
Bennis, Mohamed
Ba-M'hamed, Saadia
Garcia, Rene
Language :
English
Title :
Susceptibility and Resilience to PTSD-Like Symptoms in Mice Are Associated with Opposite Dendritic Changes in the Prelimbic and Infralimbic Cortices Following Trauma.
Publication date :
2019
Journal title :
Neuroscience
ISSN :
0306-4522
eISSN :
1873-7544
Publisher :
Elsevier, Netherlands
Volume :
418
Pages :
166-176
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
Ago Y, Hayata-Takano A, Kawanai T, Yamauchi R, Takeuchi S, Cushman JD, et al. (2017): Impaired extinction of cued fear memory and abnormal dendritic morphology in the prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice. Neurobiol Learn Mem. 145: 222–231.
Bentefour Y, Bennis M, Garcia R, Ba-M'hamed S (2018): High-frequency stimulation of the infralimbic cortex, following behavioral suppression of PTSD-like symptoms, prevents symptom relapse in mice. Brain Stimul. 11: 913–920.
Bentefour Y, Bennis M, Garcia R, M'hamed SB (2015): Effects of paroxetine on PTSD-like symptoms in mice. Psychopharmacology (Berl). 232: 2303–12.
Bentefour Y, Rakibi Y, Bennis M, Ba-M'hamed S, Garcia R (2016): Paroxetine treatment, following behavioral suppression of PTSD-like symptoms in mice, prevents relapse by activating the infralimbic cortex. Eur Neuropsychopharmacol. 26: 195–207.
Bloodgood DW, Sugam JA, Holmes A, Kash TL (2018): Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Transl Psychiatry. 60: 60–71.
Breslau N, Kessler RC (2001): The stressor criterion in DSM-IV posttraumatic stress disorder: An empirical investigation. Biol Psychiatry. 50: 699–704.
Brodnik ZD, Black EM, Clark MJ, Kornsey KN, Snyder NW, España RA (2017): Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine. Neuropharmacology. 125: 295–307.
Brown SM, Henning S, Wellman CL (2005): Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex. Cereb Cortex. 1714–1722.
Burgos-Robles A, Vidal-Gonzalez I, Quirk GJ (2009): Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J Neurosci. 29: 8474–8482.
Burnham KP, Anderson DR (2003): Model selection and multimodel inference: a practical information-theoretic approach. Springer Science & Business Media. 75–77.
Calhoun PS, Wagner HR, McClernon FJ, Lee S, Dennis MF, Vrana SR. (2011): The effect of nicotine and trauma context on acoustic startle in smokers with and without posttraumatic stress disorder. Psychopharmacology (Berl). 215: 379–389.
Carobrez AP, Bertoglio LJ (2005): Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on. Neurosci Biobehav Rev. 29: 1193–1205.
Charney DS. (2004): Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. American Journal of Psychiatry. 161: 195–216.
Cheriyan J, Kaushik MK, Ferreira AN, Sheets PL (2016): Specific targeting of the basolateral amygdala to projectionally defined pyramidal neurons in prelimbic and infralimbic cortex. eNeuro. 3:2–16.
Chilcoat HD, Breslau N (1998): Investigations of causal pathways between PTSD and drug use disorders. Addict Behav. 23: 827–840.
Cho JH, Deisseroth K, Bolshakov VY (2013): Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron. 80: 1491–1507.
Cohen H, Zohar J, Matar M, Zeev K, Loewenthal U, Richter-Levin G (2004): Setting apart the affected: The use of behavioral criteria in animal models of post traumatic stress disorder. Neuropsychopharmacology. 29: 1962–1970.
Cook SC, Wellman CL (2003): Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol. 60: 236–248.
Cordero MI, Venero C, Kruyt ND, Sandi C (2003): Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats: Evidence for a role of corticosterone. Horm Behav. 44: 338–345.
Criado-Marrero M, Morales Silva RJ, Velazquez B, Hernández A, Colon M, Cruz E, (2017): Dynamic expression of FKBP5 in the medial prefrontal cortex regulates resiliency to conditioned fear. Learn Mem. 24: 145–152.
Dopfel D, Perez PD, Verbitsky A, Bravo-Rivera H, Ma Y, Quirk GJ, Zhang N, (2019): Individual variability in behavior and functional networks predicts vulnerability using a predator scent model of PTSD. Nat Commun. 1–12.
Elharrar E, Warhaftig G, Issler O, Sztainberg Y, Dikshtein Y, Zahut R, et al. (2013): Overexpression of corticotropin-releasing factor receptor type 2 in the bed nucleus of stria terminalis improves posttraumatic stress disorder-like symptoms in a model of incubation of fear. Biol Psychiatry. 74: 827–836.
Fanselow MS, Kim JJ, Yipp J, De Oca B (1994): Differential effects of the N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues. BehavNeurosci. 108: 235–240.
Febbraro F, Svenningsen K, Tran TP, Wiborg O (2017): Neuronal substrates underlying stress resilience and susceptibility in rats. PLoS One. 12: 1–19.
Fucich EA, Paredes D, Saunders MO, Morilak DA (2018): Activity in the ventral medial prefrontal cortex is necessary for the therapeutic effects of extinction in rats. J Neurosci. 38: 1408–1417.
Giustino TF, Maren S (2015): The role of the medial prefrontal cortex in the conditioning and extinction of fear. Front Behav Neurosci. 9: 1–20.
Herry C, Garcia R (2002): Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. J Neurosci. 22: 577–583.
Herry C, Vouimba R-M, Garcia R (1999): Cortical transmission in behaving mice plasticity in the mediodorsal thalamo-prefrontal. J Neurophysiol. 82: 2827–2832.
Izquierdo A, Wellman C, Holmes A (2006): Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice. J Neurosci. 26: 5733–5738.
Jinks AL, McGregor IS (1997): Modulation of anxiety-related behaviors following lesions of the prelimbic or infralimbic cortex in the rat. Brain Res. 772: 181–190.
Kanarik M, Alttoa A, Matrov D, Kõiv K, Sharp T, Panksepp J, Harro J (2011): Brain responses to chronic social defeat stress: Effects on regional oxidative metabolism as a function of a hedonic trait, and gene expression in susceptible and resilient rats. Eur Neuropsychopharmacol. 21: 92–107.
Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995): Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 52: 1048–60.
Le Dorze C, Gisquet-Verrier P (2016a): Effects of multiple brief exposures to trauma-associated cues on traumatized resilient and vulnerable rats. Brain Res. 1652: 71–80.
Le Dorze C, Gisquet-Verrier P (2016b): Sensitivity to trauma-associated cues is restricted to vulnerable traumatized rats and reinstated after extinction by yohimbine. Behav Brain Res. 313: 120–134.
Lebow M, Neufeld-cohen A, Kuperman Y, Tsoory M, Gil S, Chen A (2012): Susceptibility to PTSD-like behavior is mediated by corticotropin-releasing factor receptor type 2 levels in the bed nucleus of the stria terminalis. J Neurosci. 32: 6906–6916.
Levkovitz Y, Fenchel D, Kaplan Z, Zohar J, Cohen H (2015): Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD. Eur Neuropsychopharmacol. 25: 124–132.
Maier SF, Watkins LR (2010): Role of the medial prefrontal cortex in coping and resilience. Brain Res. 1355: 52–60.
McDonald A, Mascagni F, Guo L (1996): Projections of the medial and lateral prefontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience. 71: 55–75.
Milad MR, Quirk GJ (2002): Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 420: 713–717.
Moench KM, Maroun M, Kavushansky A, Wellman C (2016): Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress. Neurobiol Stress. 3: 23–33.
Monfils MH, VandenBerg PM, Kleim JA, Teskey GC (2004): Long-term potentiation induces expanded movement representations and dendritic hypertrophy in layer v of rat sensorimotor neocortex. Cereb Cortex. 14: 586–593.
Muller D, Toni N, Buchs PA (2000): Spine changes associated with long-term potentiation. Hippocampus. 10: 596–604.
Nalloor R, Bunting K, Vazdarjanova A (2011): Predicting impaired extinction of traumatic memory and elevated startle. PLoS One.600:19760.
Olatunji BO, Fan Q, Wolitzky-Taylor K (2018): Anxiety sensitivity and post-traumatic stress reactions: Effects of time-varying intrusive thoughts and associated distress. J BehavTherExp Psychiatry. 61: 113–120.
Quirk GJ, Likhtik E, Pelletier JG, Paré D (2003): Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci. 23: 8800–7.
Radley JJ, Rocher AB, Miller M, Janssen WGM, Liston C, Hof PR, et al.(2006): Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex. 16: 313–320.
Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, et al. (2004): Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience. 125: 1–6.
Rao RM, Sadananda M (2016): Influence of state and / or trait anxieties of wistar rats in an anxiety paradigm. Ann Neurosci. 23: 44–50.
Rau V, Fanselow MS (2009): Exposure to a stressor produces a long lasting enhancement of fear learning in rats. Stress. 12: 125–133.
Rothbaum BO, Davis M (2003): Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci. 1008: 112–121.
Santos-Anderson RM, Routtenberg A (1976): Stimulation of rat medial or sulcal prefrontal cortex during passive avoidance learning selectively influences retention performance, Brain Res. 103: 243–259.
Sheynin J, Shind C, Radell M, Ebanks-Williams Y, Gilbertson MW, Beck KD, Myers CE (2017): Greater avoidance behavior in individuals with posttraumatic stress disorder symptoms. Stress. 20: 285–293.
Siegmund A, Wotjak CT (2007): A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitized fear. J Psychiatr Res. 41: 848–860.
Sillivan SE, Joseph NF, Jamieson S, King ML, Chévere-Torres I, Fuentes I, et al. (2017): Susceptibility and resilience to posttraumatic stress disorder–like behaviors in inbred mice. Biol Psychiatry. 82: 924–933.
Sun D, Davis SL, Haswell CC, Swanson CA, LaBar KS, Fairbank JA, et al. (2018): Brain structural covariance network topology in remitted posttraumatic stress disorder. Front Psychiatry. 9: 1–10.
Toledano D, Gisquet-Verrier P (2014): Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: An effect abolished by a single amphetamine injection. Behav Brain Res. 272: 165–174.
Yehuda R, LeDoux J (2007): Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron. 56: 19–32.
